ABSTRACT Despite significant increases in global health investment and the availability of low-cost, efficacious interventions designed to reduce the burden of preventable diseases in low and middle income countries, the translation of these scientific advances into effective delivery strategies has been slow, uneven and incomplete. Health systems play a fundamental role in closing this gap between our scientific knowledge and their delivery at sufficient scale to lead to population-level improvements in health outcomes. However, the complexity of health systems continues to challenge implementation researchers and their efforts to identify and overcome health system barriers, and broadly apply these lessons learned. This goal of this research project, funded through the Doris Duke Charitable Foundation's African Health Initiative, is to improve health outcomes in 13 districts in Sofala province, Mozambique, through strengthened health systems and delivery of integrated primary health care. In specific aim 1, we will assess health systems strengthening interventions including improved data systems, use of data driven decision-making tools, and strengthened leadership and management capacity of district health teams on health system outputs and outcomes. In specific aim 2 we will assess the impact of a package of health systems strengthening interventions including improved data systems, use of data driven decision-making tools, and strengthened leadership and management capacity of district health teams on population-level health outcomes. A quasi-experimental design will be employed to respond to the specific aims, comparing changes in output, outcome and impact measures selected to capture service delivery and health outcome improvements. The results of this implementation research will generate knowledge of global significance to support evidence-based health delivery and health systems planning.